在体内,单细胞CRISPR揭示了瘤进化中的特异性TNF程序
Peter F Renz1, Umesh Ghoshdastider1, Simona Baghai Sain2
1Institute for Regenerative Medicine (IREM), University of Zurich, Schlieren-Zurich, Switzerland.
Nature
|July 17, 2024
概括
这项研究揭示了瘤死因 (TNF) 在癌症演变过程中的不同信号程序. 一个新的体内CRISPR屏幕识别了TNF信号作为状细胞癌的克隆扩张和入侵的驱动因素.
科学领域:
- 癌症生物学
- 遗传学
- 免疫学
背景情况:
- 瘤生成涉及由突变驱动的克隆扩张,但导致恶性转变的机制尚不清楚.
- 了解正常组织中的克隆动态对于破译早期癌症发展至关重要.
研究的目的:
- 在体内使用单细胞CRISPR系统地研究瘤进化过程中的全组织克隆动态和基因程序.
- 发现导致细胞癌扩散和恶性转变的机制.
主要方法:
- 开发了一种体内单细胞CRISPR策略与超声波导向的子宫内微注射.
- 通过单细胞RNA测序和指导捕获利用纵向监测来分析克隆扩张.
- 研究了150个经常发生突变的状细胞癌基因的作用.
主要成果:
- 鉴定了一种瘤亡因子 (TNF) 信号模块,涉及TNF受体1和巨细胞,作为表皮组织中克隆扩张的驱动因素.
- 在瘤形成过程中观察到TNF信号模块的下调,转换为侵袭性癌细胞的TNF程序.
- 证明自性TNF程序调解侵袭性质,并与患者的生存时间缩短相关.
结论:
- 在体内单细胞CRISPR查是研究哺乳动物组织动态的强大工具.
- 独特的TNF信号程序在瘤进化,克隆扩张和入侵中发挥着关键作用.
- 了解克隆扩张和瘤发生之间的相互作用对于癌症研究至关重要.
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